Methods for detecting cancer include a method of detecting a cancer-specific antigenic substance in blood, a method of identifying a cancer specific genetic change by a DNA amplification method or the like, and other methods. These are methods, in which cancer is detected using a cancer-specific antigenic substance existing in blood or a cancer-specific genetic change as a tumor marker.
As such cancer-specific antigenic substances existing in blood, there are many types of antigenic substances such as a glycoprotein, a hormone and an enzyme. Among these substances, those which have been actively applied in clinical sites include a prostate specific antigen (PSA), a carcinoembryonic antigen (CEA), CA19-9, CA50, Span-1, Dupan-2 and the like.
Moreover, as such cancer-specific genetic changes, cancer-specific sequences found in a RAS oncogene or a BRCA1 cancer suppressor gene haven been known, for example. An attempt to use these cancer-specific sequences as tumor markers has gradually progressed.
However, conventional tumor markers have room for improvement in terms of cancer detection rates and false positive rates. For example, CEA and CA19-9, which are used as tumor markers for colon cancer, also exhibit high values due to the inflammation of a digestive system, such as hepatitis and pancreatitis. Thus, there is a fear that these tumor markers detect the inflammation of a digestive system incorrectly as colon cancer. Furthermore, there exist tumors (negative tumors) that cannot be detected by CEA or CA19-9, although they are colon cancers.
Patent Document 1 describes a method for detecting cellular proliferative disease, which comprises allowing a reagent for detecting the methylation of polynucleotide p16 to come into contact with cells in tissues.
Patent document 2 describes a method for detecting the methylation of DNA, using Methylation Specific PCR (MSP).
Patent Document 3 describes a method for detecting the methylation of a cytosine residue, using Methylation-Sensitive Single Nucleic Primer Extension (Ms-SNuPE).
Patent Document 4 describes a method for detecting the methylation of genomic DNA. In this method, target DNA in the genomic DNA is amplified, while maintaining the methylated state thereof, and the amplified DNA is then analyzed using a mass spectrometer, so as to detect the methylation of the target DNA.
Non-Patent Document 1 describes that a ZAR1 gene in the ovum of mother is an important gene essential for the early stage at which a fertilized ovum is matured to become an embryo.
Non-Patent Document 2 describes that such ZAR1 gene is well preserved as an expression gene specific to the ovary of a vertebrate animal.